Research Article
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Published Online: 29 June 2009

Skin-Derived Precursors Differentiate Into Skeletogenic Cell Types and Contribute to Bone Repair

Publication: Stem Cells and Development
Volume 18, Issue Number 6

Abstract

Skin-derived precursors (SKPs) are multipotent dermal precursors that share similarities with neural crest stem cells and that can give rise to peripheral neural and some mesodermal cell types, such as adipocytes. Here, we have asked whether rodent or human SKPs can generate other mesenchymally derived cell types, with a particular focus on osteocytes and chondrocytes. In culture, rodent and human foreskin–derived SKPs differentiated into alkaline-positive, collagen type-1-positive, mineralizing osteocytes, and into collagen type-II-positive chondrocytes that secreted chondrocyte-specific proteoglycans. Clonal analysis demonstrated that SKPs efficiently generated these skeletogenic cell types, and that they were multipotent with regard to the osteogenic and chondrogenic lineages. To ask if SKPs could generate these same lineages in vivo, genetically tagged, undifferentiated rat SKPs were transplanted into a tibial bone fracture model. Over the ensuing 6 weeks, many of the transplanted cells survived within the bone callus, where they were morphologically and phenotypically similar to the endogenous mesenchymal/osteogenic cells. Moreover, some transplanted cells adopted a mature osteocyte phenotype and integrated into the newly formed bone. Some transplanted cells also differentiated into chondrocytes and into smooth muscle cells and/or pericytes that were associated with blood vessels. Thus, both rodent and human SKPs generate skeletogenic cell types in culture, and the injured bone environment is sufficient to instruct SKPs to differentiate down an osteogenic lineage, in a fashion similar to the endogenous mesenchymal precursors.

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cover image Stem Cells and Development
Stem Cells and Development
Volume 18Issue Number 6July/August 2009
Pages: 893 - 906
PubMed: 18834279

History

Published in print: July/August 2009
Published online: 29 June 2009
Published ahead of print: 7 May 2009
Published ahead of production: 3 October 2008

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Jean-Francois Lavoie
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Jeffrey A. Biernaskie
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Yan Chen
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Darius Bagli
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Benjamin Alman
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
David R. Kaplan
Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Freda D. Miller
Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.

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